1434 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. 18, NO. 4, JULY/AUGUST 2012 Laser Immunotherapy: Concept, Possible Mechanism, Clinical Applications, and Recent Experimental Results Xiaosong Li, Min Min, Ying Gu, Nan Du, Tomas Hode, Robert E. Nordquist, Roman F. Wolf, Eric Howard, John A. Lunn, Orn Adalsteinsson, and Wei R. Chen (Invited Paper) Abstract—Laser immunotherapy (LIT) is an in situ autologous cancer vaccine (inCVAX) that induces a systemic immune re- sponses through a local intervention. The effect of LIT depends on two major interactions: a selective photothermal interaction and an active immunological stimulation. The selective photothermal interaction can help release tumor antigens, which can stimulate specific antitumor immunity in the host. The elevated expression of heat-shock protein and the local application of immunoadjuvant further enhance the immune responses. The safety and effective- ness of LIT have been tested in preclinical studies and in prelim- inary clinical trials. Tumor samples from breast cancer patients treated by LIT were analyzed using histochemical methods. Pre- liminary results showed a change in T cells after LIT treatment, indicating strong induced immune responses. LIT may be proven to be a feasible treatment modality for metastatic cancers. Index Terms—Breast cancer, cancer immunotherapy, im- munoadjuvant, laser treatment, photothermal interaction. Manuscript received September 6, 2011; revised October 31, 2011 and De- cember 8, 2011; accepted December 11, 2011. Date of publication December 30, 2011; date of current version July 10, 2012. This work was supported in part by grants from the U.S. National Institutes of Health (P20 RR016478 from the INBRE Program of the National Center for Research Resources) and by the National Natural Science Foundation of China (Grant 81000994). X. Li and M. Min contributed equally to this work. X. Li is with the Department of Oncology, First Affiliated Hospital of Chinese PLA General Hospital and the Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, China. M. Min is with the Department of Gastroenterology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China (e-mail: minmin823@sina.com). Y. Gu is with the Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, China. N. Du is with the Department of Oncology, First Affiliated Hospital of Chi- nese PLA General Hospital, Beijing 100048, China. T. Hode and R. E. Nordquist are with the ImmunoPhotonics Inc., Columbia, MO 65211 USA. R. F. Wolf is with the Department of Comparative Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA. E. Howard is with the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA. J. A. Lunn is with the Commonwealth Medical Research Institute, Nassau, The Bahamas. O. Adalsteinsson is with the International Strategic Cancer Alliance, Kennett Square, Philadelphia, PA 19348 USA. W. R. Chen is with the Department of Engineering and Physics, University of Central Oklahoma, Edmond, OK 73034 USA (e-mail: wchen@uco.edu). Digital Object Identifier 10.1109/JSTQE.2011.2182183 I. INTRODUCTION T HE ideal cancer therapy should not only destroy the tumor, but also at the same time trigger the immune system to rec- ognize, track down, and destroy any remaining tumor cells, be they at or near the site of the primary tumor or distant metas- tases [1]. Systemic antitumor immunity may be induced after local treatment by many different ablative techniques. Local cancer treatment modalities such as radiofrequency, laser, mi- crowave, and photodynamic therapy (PDT) have been shown to lead to local destruction of primary tumors as well as to in- duction of antitumor immune response [1]–[5]. For example, PDT can cause acute inflammation, expression of heat-shock proteins (HSPs), invasion and infiltration of the treated tumor by leukocytes, and might increase the presentation of tumor- derived antigens to T cells [1]. It is believed that tumor cells processed by ablative techniques could function as sources of in situ autologous whole-cells cancer vaccine. Laser immunotherapy (LIT) was proposed based on the same principle in 1997 [6]. LIT provides a convenient, efficient way to generate personalized tumor-specific immunity. LIT contains two major components: 1) a near-infrared laser for tumor irradiation, either applied directly through an interstitial fiber, or in combination with a light-absorbing agent such as indocyanine green (ICG), and 2) glycated chitosan (GC, a proprietary immunoadjuvant) [7], [8]. Both components of LIT contribute to the antitumor immune response. In the present study, ICG (absorption peak at 800±5 nm) was injected into the center of the tumor to enhance laser light absorption, followed by a topical application of a diode laser emitting 805-nm light to induce a selective photothermal effect (the light was delivered through an optical fiber connected to a handpiece, which in turn was placed in contact with the skin above the location of the tumor where ICG was injected). GC, as an immunoadjuvant, is injected into the center of the tumor and/or around the tumor to further stimulate the immune response. Animal studies using LIT showed that the combination of the selective photothermal and immunological interactions, both ap- plied locally, could not only destroy the treated primary tumors but also eradicate untreated metastases at distant sites [9], [10]. Investigator-driven clinical trials using LIT for the treatment of metastatic melanoma and breast cancer are under way and the preliminary clinical outcome is very promising. 1077-260X/$26.00 © 2011 IEEE